Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease
Authors
Nicolai Franzmeier, Klinikum der Universität München
Julia Neitzel, Klinikum der Universität München
Anna Rubinski, Klinikum der Universität München
Ruben Smith, Skånes universitetssjukhus
Olof Strandberg, Institutionen för Kliniska Vetenskaper, Malmö
Rik Ossenkoppele, Institutionen för Kliniska Vetenskaper, Malmö
Oskar Hansson, Institutionen för Kliniska Vetenskaper, Malmö
Michael Ewers, Klinikum der Universität München
Michael Weiner, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
William Jagust, University of California, Berkeley
John Q. Trojanowki, University of Pennsylvania
Arthur W. Toga, USC
Laurel Beckett, University of California, Davis
Robert C. Green, Harvard Medical School
Andrew J. Saykin, Indiana University Bloomington
John C. Morris, Washington University in St. Louis
Leslie M. Shaw, University of Pennsylvania
Enchi Liu, Janssen Alzheimer Immunotherapy
Tom Montine, University of Washington
Ronald G. Thomas, University of California, San Diego
Michael Donohue, University of California, San Diego
Michael Donohue, University of California, San Diego
Sarah Walter, University of California, San Diego
Devon Gessert, University of California, San Diego
Tamie Sather, University of California, San Diego
Gus Jiminez, University of California, San Diego
Danielle Harvey, University of California, Davis
Matthew Bernstein, Mayo Clinic
Nick Fox, University of London
Publication Date
12-1-2020
Journal
Nature Communications
URL with Digital Object Identifier
10.1038/s41467-019-14159-1
Abstract
In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (BioFINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.
